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Circ‐LRP6 mediates epithelial‐mesenchymal transition and autophagy in oral squamous cell carcinomas

Qian Zhang, Chunmiao Jiang, Wenhao Ren, Shaoming Li, Jingjing Zheng, Yuli Gao, Keqian Zhi, Ling Gao

2021Journal of Oral Pathology and Medicine14 citationsDOI

Abstract

BACKGROUND: Tumor metastasis seriously affects the therapeutic effect and prognosis of cancer patients. Here, we studied the role of has_circ_0000378 (circ-LRP6) in oral squamous cell carcinoma (OSCC) metastasis to explore new ideas and schemes for clinical treatment. METHODS: The expressions of circ-LRP6 in OSCC and normal tissues from matched controls were measured by real-time PCR (RT-PCR). Levels of epithelial-mesenchymal transition (EMT) transcription factors, P62 and LC3B, were determined by Western blot analysis and immunofluorescence (IF) assay. Furthermore, we evaluated the effects of circ-LRP6 downregulation on migration, invasion, and autophagy using CCK8, transwell assays, transmission electron microscopy (TEM), and immunofluorescence (IF) assay. RESULTS: The expression of circ-LRP6 in OSCC tissues was high. Downregulation of circ-LRP6 reduced the EMT process of SCC-15 cells, as evidenced by increased E-cadherin and decreased vimentin and Zeb1 levels. Downregulation of circ-LRP6 also decreased autophagy as shown by increased levels of P62 and decreased LC3B in SCC-15 cells. Autophagy revulsant rapamycin (RAPA) rescued the inhibitory effect of circ-LRP6 on LC3B, vimentin, and Zeb1. CONCLUSIONS: circ-LRP6 promoted EMT and autophagy of OSCC and increased autophagy could rescue EMT in OSCC cells inhibited by circ-LRP6 siRNA.

Topics & Concepts

Downregulation and upregulationAutophagyEpithelial–mesenchymal transitionVimentinCancer researchMetastasisChemistryCateninWestern blotBiologyWnt signaling pathwayPathologyImmunohistochemistryMedicineCancerCell biologyInternal medicineApoptosisSignal transductionBiochemistryGeneCircular RNAs in diseasesAutophagy in Disease and TherapyWnt/β-catenin signaling in development and cancer